In a 2009 interview, Gutfeld explained that he started to experience a change in his political thinking while he was attending UC Berkeley:[8]

I became a conservative by being around liberals (at UC Berkeley) and I became a libertarian by being around conservatives. You realize that there's something distinctly in common between the two groups, the left and the right; the worst part of each of them is the moralizing.

After college he had an internship at The American Spectator, as an assistant to conservative writer R. Emmett Tyrrell. He then worked as a staff writer at Prevention magazine and in Emmaus, Pennsylvania, as an editor at various Rodale Press magazines. In 1995 he became a staff writer at Men's Health. He was promoted to editor in chief of Men's Health in 1999. A year later, he was replaced by David Zinczenko. Gutfeld then became editor in chief of Stuff, increasing circulation from 750,000 to 1.2 million during his tenure. In 2003 he hired several dwarfs to attend a conference of the "Magazine Publishers of America" on the topic of "buzz", with instructions to be as loud and annoying as possible. The stunt generated publicity but led to Gutfeld's being fired soon afterward; he was then made head of "brain development" at Dennis Publishing.[7]

He edited Maxim magazine in the UK from 2004 to 2006.[7] Gutfeld's contract expired without renewal after losses in readership under his tenure.[9]

Gutfeld was one of the first posting contributors to The Huffington Post from its launch in 2005 until October 2008; frequent targets of his sarcasm included his colleagues Deepak Chopra, Cenk Uygur, Arianna Huffington, and Huffington Post bloggers. Many of his Huffington Post commentaries/blogs are available on its website.[10] Gutfeld has his own blog site, The Daily Gut.

Beginning on February 5, 2007, Gutfeld hosted the hour-long Fox News Channel late-night program, Red Eye w/ Greg Gutfeld. From 2007 to 2013, Bill Schulz served as Gutfeld's "sidekick" and Andy Levy as the show's ombudsman. Schulz was Gutfeld's colleague at Stuff magazine and Levy was a fellow blogger at The Huffington Post. On July 11, 2011, Gutfeld became a co-host/panelist on the Fox News political opinion discussion program The Five. The program airs weekdays at 5 p.m. ET.[11] Gutfeld left Red Eye in February 2015, to host a new weekend show on Fox News.[12] He was replaced on Red Eye by Tom Shillue. In May 2015, it was announced that Gutfeld would be getting his own late-night show called The Greg Gutfeld Show, which debuted on May 31, at 10 p.m. ET.

In a five-minute segment broadcast on Tuesday, March 17, 2009, Gutfeld and his panel discussed Canadian Lieutenant General Andrew Leslie's statement that the Canadian Armed Forces may require a one-year "synchronized break" once Canada's mission in Afghanistan ends in 2011.[13] "Meaning, the Canadian military wants to take a breather to do some yoga, paint landscapes, run on the beach in gorgeous white Capri pants," Gutfeld said.[13] "I didn't even know they were in the war", comedian panelist Doug Benson added, then continued, "I thought that's where you go if you don't want to fight. Go chill in Canada."[13] Gutfeld also said: "Isn't this the perfect time to invade this ridiculous country? They have no army!"[13]

The segment drew wide attention and outrage in Canada after being posted on YouTube following the reported deaths of four Canadian soldiers in Afghanistan three days earlier.[14][15][16] Canada, at the time, had been in command of the NATO mission in the Kandahar Province, the birthplace and former capital of the Taliban, for the past three years.[17] Along with the Helmand Province, the two provinces were "home to some of the fiercest opposition to coalition forces" and reported to "have the highest casualty rates per province."[18]

Canadian Defence Minister Peter MacKay called on Fox to apologize for the satirical comments, describing the remarks as "despicable, hurtful and ignorant."[19] Gutfeld in response maintained the show is satirical and irreverent[20] but offered the following apology: "The March 17 episode of Red Eye included a segment discussing Canada's plan for a 'synchronized break,' which was in no way an attempt to make light of troop efforts. However, I realize that my words may have been misunderstood. It was not my intent to disrespect the brave men, women and families of the Canadian military, and for that I apologize."[19]

On August 9, 2010, Gutfeld stated that he planned on constructing New York City's first Islamic-friendly gay bar next to the Park51 Islamic community center, known at the time as Cordoba House and often referred to as the "Ground Zero mosque" in the media.[21][22][23][24][25] As stated in his Greg-alogue, which was featured on Red Eye: "As an American, I believe they have every right to build the mosque—after all, if they buy the land and they follow the law—who can stop them? Which is why, in the spirit of outreach, I've decided to do the same thing. I'm announcing tonight that I am planning to build and open the first gay bar that caters not only to the west, but also to Islamic gay men. I hope the mosque owners will be as open to the bar, as I am to the new mosque. After all, the belief driving them to open their Islamic center near Ground Zero is no different than mine...tolerance and understanding." Gutfeld later messaged the Park51 developers of the mosque, seeking a response to his idea. The Park51 group "tweeted" back, "You’re free to open whatever you like. If you won’t consider the sensibilities of Muslims, you’re not going to build dialog."[26] After that Park51 tweet, Gutfeld announced he wanted to build his establishment and name it Dialogue. Other names for the proposed gay bar were sent in to the Red Eye host (via Twitter and the Internet) by fans, such as: al Gayda, Grind Zero, The Holey Land, You Mecca Me Hot, and Jihard. Gutfeld has stated he supports the constitutional right of anyone to build a mosque on that site; however, some feel the question of sensitivity toward New Yorkers and Americans who were the targets and victims on 9-11 should be addressed first.[26]

As of 2012[update], Gutfeld resides in New York City with his wife, Elena Moussa, whom he met in London, where he lived for three years.[8][27] Gutfeld was raised Catholic and once was an altar boy.[28]